reproductive number during acute HIV-1 infection

Estimation of the initial viral growth rate and the basic reproductive number during acute HIV-1 infection

During primary infection, the number of HIV-1 virus particles in plasma increases rapidly, reaches a peak and then declines until it reaches a set-point level. Understanding the kinetics of primary infection, and its effect on the establishment of chronic infection, is important in defining the early pathogenesis of HIV. The authors studied the viral dynamics of very early HIV-1 infection in 47 subjects identified through plasma donation screening. They calculate how fast the viral load increases and how variable this parameter is among individuals. They also estimate the basic reproductive ratio, the number of new infected cells generated by an infectious cell at the start of infection when target cells are not limiting. The initial viral doubling time has a median of 0.65 days with interquartile range 0.56 - 0.91 days. The median basic reproductive ratio was 8.0 with interquartile range 4.9 - 11. In 15 patients, they also observed the decay of plasma virus post-peak and found that the virus decay occurred at a median rate of 0.60 day (-1), corresponding to a half-life of 1.2 days. The median peak viral load was 5.8 log10 HIV-1 RNA copies/ml and it was reached 14 days after virus was quantifiable with an assay with a lower limit of detection of 50 copies/ml. These results characterize the early plasma viral dynamics in acute HIV infection better than it has been possible thus far. They also define better the challenge that the immune response (or therapeutic intervention) has to overcome to defeat HIV at this early stage.

Editors’ note: We need to learn much more about what happens in those first days after HIV exposure when HIV may get a toehold. Our own immune responses seem too little too late in the race between the immune system and the virus. This study of people in very early infection calculated the basic reproductive ratio of the virus, meaning how many cells one virus can infect if there is no limit on the number of available target cells. This was possible because the researchers had viral load measurements on the subjects from before the initial peak in viral load was reached. Their findings suggest that in order for a vaccine to bring the basic reproductive ratio down to below 1 so that a majority of HIV-exposed people would not become infected, it would have to be 90% effective in reducing viral growth. That’s a pretty tall order!